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Hypoxia, but not reoxygenation, induces interleukin 6 gene expression through NF-kappa B activation.

Abstract
Interleukin (IL) 6 is one of major mediators of inflammation, and IL-6 gene activation during hypoxia/reoxygenation has been implicated in the pathogenesis of ischemia/reperfusion injury. However, molecular events involved in IL-6 gene expression during hypoxia/reoxygenation remain to be identified. We have previously shown that NF-kappa B plays an essential and indispensable role in the transcriptional activation of the IL-6 gene induced by various stimuli, including IL-1 and tumor necrosis factor-alpha. We show here that hypoxia, but not reoxygenation, induces the activation of NF-kappa B through the degradation of a major inhibitor of NF-kappa B, I kappa B alpha. This hypoxia-induced NF-kappa B activation resulted in the kappa B-dependent transcriptional activation of the IL-6 gene. Interestingly, the time course of hypoxia-induced NF-kappa B activation was rather slow as compared with those of NF-kappa B activation induced by other stimuli, such as IL-1: a significant NF-kappa B activation was not observed before 1 hr of hypoxia treatment and persisted for up to 7 hr of hypoxia treatment. However, hypoxia-induced NF-kappa B activation was not inhibited by cycloheximide, which indicates that hypoxia directly triggers NF-kappa B activation. Furthermore, while hypoxia is unlikely to generate reactive oxygen intermediates, pretreatment of cells with antioxidants such as N-acetyl cysteine and alpha-tocopherol inhibited NF-kappa B activation induced by hypoxia. Thus, we discuss possible implications of these results for a postulated role of reactive oxygen intermediates in NF-kappa B activation.
AuthorsK Muraoka, K Shimizu, X Sun, Y K Zhang, T Tani, T Hashimoto, M Yagi, I Miyazaki, K Yamamoto
JournalTransplantation (Transplantation) Vol. 63 Issue 3 Pg. 466-70 (Feb 15 1997) ISSN: 0041-1337 [Print] United States
PMID9039941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-6
  • NF-kappa B
  • Reactive Oxygen Species
  • Oxygen
Topics
  • Animals
  • Gene Expression Regulation (immunology)
  • Hypoxia (etiology, genetics, metabolism)
  • Interleukin-6 (genetics)
  • L Cells
  • Mice
  • NF-kappa B (metabolism)
  • Oxygen (metabolism)
  • Reactive Oxygen Species (physiology)
  • Reperfusion Injury (genetics, immunology, metabolism)
  • Transcription, Genetic (immunology)
  • Transcriptional Activation

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